This event brings together specialists from Process Development, Analytical Characterization, CMC, and Regulatory Strategy amongst others to examine the important interface between the process, vaccine characterization, and interaction with the regulatory authorities. Attendees will discover how the experts adapt the process and set up panels of characterization tests for robust potency assays, physicochemical characterization, and for release. We plan to cover all stages of development, a range of prophylactic areas, a selection of cell lines and a variety of vaccines.

The current production process for BioThrax® (Anthrax Vaccine Adsorbed) is based on 1960’s technology, has remained relatively unchanged, and is executed at a scale that does not permit Emergent BioSolutions to meet the USG’s stated requirement of 75 million doses of a general use prophylaxis vaccine for the prevention of anthrax. Emergent Biosolutions has built a modern facility for the production of BioThrax; included a 12 fold increase in scale, a number of process improvements designed to increase process control, and capability of meeting the US government requirement of 75 million doses.

We have designed virus-like particle (VLP) vaccine “virosome” technology specifically for the development of safe and effective subunit vaccines. Virosomes are particularly well suited for addressing new vaccine indications. The transition of our current vaccine candidate against recurrent vulvovaginal candidiasis (RVVC) from the bench-scale to the CTM production will be reviewed, with focus on upscaling and change implementation.

2:50 Technology Transfer during Facility Construction – A Real Life Story at Medicago

Medicago is expanding the production capacity for its Nicotianabenthamiana-based vaccine production platform. This expansion included building a facility in Research Triangle Park, NC on a tight timeline, scaling the process approximately 30-fold and transferring the production technology to the new facility from Quebec City, Canada. In addition, the project was tied to deliverables for DARPA which included the promise of producing 10 million vaccine doses within a 30-day period to demonstrate the success of the construction and technology transfer operations. The challenges and successes of the project will be reviewed and examples of lessons learned will be presented.

FluBlok® is a recombinant trivalent influenza vaccine produced using the baculovirus expression system. The vaccine is currently under regulatory review by the FDA. The technical, quality and regulatory challenges of adapting to seasonal influenza strain changes are magnified by the desire to also implement process improvements for more efficient production. This case-study will examine options for future FluBlok yield improvements and the strategies for evaluating their benefits and risks from process development, manufacturing, quality and regulatory perspectives.

We have developed a downstream manufacturing process to enable DNA vaccines simultaneously targeting multiple antigens and/or pathogens. The process includes a streamlined recovery process, highly selective plasmid capture and polishing chromatography steps, and transmembrane filtration for plasmid concentration. The end result is a process that is readily scalable to commercial capacities and final drug products that are highly reproducible and easily characterized through validated assays. Products manufactured using this process have translated into human clinical trials for multivalent HPV therapy and seasonal/avian influenza.

The biopharmaceutical development and manufacturing strategy for a vaccine are guided by the product’s quality target product profile (QTPP). Quality by Design (QbD) principles are applied from the onset of product definition and development, and intended to ensure that the product is designed to meet patient safety and efficacy requirements. Potential CQAs are selected on the basis of prior knowledge and current understanding of structure-function relationships, and a risk-assessment tool is developed and applied to each quality attribute. CMC-related activities focus on refining structure-function relationships and their impact on safety and efficacy; this information is used to iteratively update the CQA risk assessments throughout the product lifecycle.